DTU Nanotech is currently developing containers smaller than a grain of sugar to be able to lead benign bacteria safely through the gastric acid for release in the mucous membrane of the intestines.

An imbalance in the composition of bacteria in the mucous membrane of the intestines has great influence on a series of serious diseases such as e.g. colitis. More than 20,000 Danes suffer from this condition of inflammation in the mucous membrane of the large intestine. It is difficult to reestablish the composition of the bacteria in the intestinal system once it has become unbalanced, and the methods used today are not especially effective.

“In our project, we examine a new method which will make it possible to reestablish the balance in the system simply by taking a tablet”, says Professor Anja Boisen from IDUN – Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics, at DTU Nanotech.

Anja Boisen was recently granted 15 MDKK from the Novo Nordisk Foundation to further develop the small microcontainers, which are to carry the living, beneficial bacteria to the mucous membrane of the intestines, in order to reestablish the bacterial balance. The project is conducted in collaboration with a research group at DTU Food with expertise in intestinal microbiology.

Fabrication of powdered bacteria

DTU Food’s role is among other things to produce healthy lactic acid bacteria which are to contribute to the balance in the system. Nutrients and stabilising substances added to the bacteria form the basis of the powder added to the microcontainers. The powder is added by placing a mask over the microcontainers and pushing the open part of the microcontainers into the powder. “Afterwards we place a lid on the microcontainers in order to protect the bacteria on their way through the stomach”, Anja Boisen explains.

In the prototype of the new capsule, there are hundreds of microcontainers with healthy bacteria in micro amounts. When the patient swallows the capsule, its gelatin shell will be dissolved when it passes through the stomach and the small medicine capsules will enter the intestines where they will attach themselves and deliver the medicine directly in the wall of the intestines, whence it is absorbed into the body. This way the medicine is delivered directly where it is needed and in much smaller quantities than now.
(c) Technical University of Denmark

The idea is that a patient is to ingest the microcontainers via a regular capsule. Therefore hundreds of microscopic containers with very small amounts of bacteria are placed in gelatin capsules similar to those known from other medicinal products. The gelatin capsule is able to withstand the trip through the oesophagus into the stomach, where it is dissolved.

Researchers have designed the microcontainers with a lid of the pH sensitive material Eudragit which does not react with the acid in the stomach and does not dissolve until it reaches the pH neutral environment in the intestines. When the lid of the containers is gone, the bacteria spread into the mucous membrane of the intestines. However, there is a further need for developing the advanced materials – the polymer – of which the containers are made.

“The microcontainers are produced in the clean room at DTU Danchip (the national center for micro and nanofabrication red.). For now they are produced using the polymer SU-8 which is UV sensitive but not biodegradable”, Anja Boisen explains. “We have been working with this polymer for several years now and have considerable experience with it. However, we would like to move to a biodegradable polymer. These have better future prospects in that they will gain approval from the authorities more easily, should we reach that stage.”

One of the great challenges in the project is therefore to produce microcontainers which both have the abilities to carry drugs – or as in this case bacteria – and at the same time are able to erode in the intestines without affecting the system negatively. “We would like to use PCL (polycaprolactone), as it has a relatively long erosion time and good properties with regard to the processes we use for the microcontainers. But it takes time to readjust the production for the new polymers. First we will test them in agar-plates with pieces of pigs’ intestines and later with those from mice. Further down the road, the method may make it possible for patients to simply swallow a capsule to reestablish the balance in the intestines”, Anja Boisen says.

Source: Technical University of Denmark